8cxf
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8cxf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CXF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CXF FirstGlance]. <br> | <table><tr><td colspan='2'>[[8cxf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CXF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CXF FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CBR:5-BROMO-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>CBR</scene>, <scene name='pdbligand=PG5:1-METHOXY-2-[2-(2-METHOXY-ETHOXY]-ETHANE'>PG5</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.77Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CBR:5-BROMO-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>CBR</scene>, <scene name='pdbligand=PG5:1-METHOXY-2-[2-(2-METHOXY-ETHOXY]-ETHANE'>PG5</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8cxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cxf OCA], [https://pdbe.org/8cxf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cxf RCSB], [https://www.ebi.ac.uk/pdbsum/8cxf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cxf ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8cxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cxf OCA], [https://pdbe.org/8cxf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cxf RCSB], [https://www.ebi.ac.uk/pdbsum/8cxf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cxf ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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An i-motif is a non-canonical DNA structure implicated in gene regulation and linked to cancers. The C-rich strand of the HRAS oncogene, 5'-CGCCCGTGCCCTGCGCCCGCAACCCGA-3' (herein referred to as iHRAS), forms an i-motif in vitro but its exact structure was unknown. HRAS is a member of the RAS proto-oncogene family. About 19 % of US cancer patients carry mutations in RAS genes. We solved the structure of iHRAS at 1.77 A resolution. The structure reveals that iHRAS folds into a double hairpin. The two double hairpins associate in an antiparallel fashion, forming an i-motif dimer capped by two loops on each end and linked by a connecting region. Six C-C(+) base pairs form each i-motif core, and the core regions are extended by a G-G base pair and a cytosine stacking. Extensive canonical and non-canonical base pairing and stacking stabilizes the connecting region and loops. The iHRAS structure is the first atomic resolution structure of an i-motif from a human oncogene. This structure sheds light on i-motifs folding and function in the cell. | An i-motif is a non-canonical DNA structure implicated in gene regulation and linked to cancers. The C-rich strand of the HRAS oncogene, 5'-CGCCCGTGCCCTGCGCCCGCAACCCGA-3' (herein referred to as iHRAS), forms an i-motif in vitro but its exact structure was unknown. HRAS is a member of the RAS proto-oncogene family. About 19 % of US cancer patients carry mutations in RAS genes. We solved the structure of iHRAS at 1.77 A resolution. The structure reveals that iHRAS folds into a double hairpin. The two double hairpins associate in an antiparallel fashion, forming an i-motif dimer capped by two loops on each end and linked by a connecting region. Six C-C(+) base pairs form each i-motif core, and the core regions are extended by a G-G base pair and a cytosine stacking. Extensive canonical and non-canonical base pairing and stacking stabilizes the connecting region and loops. The iHRAS structure is the first atomic resolution structure of an i-motif from a human oncogene. This structure sheds light on i-motifs folding and function in the cell. | ||
| - | Crystal Structure of an i-Motif from the HRAS Oncogene Promoter.,Li KS, Jordan D, Lin LY, McCarthy SE, Schneekloth JS Jr, Yatsunyk LA Angew Chem Int Ed Engl. 2023 | + | Crystal Structure of an i-Motif from the HRAS Oncogene Promoter.,Li KS, Jordan D, Lin LY, McCarthy SE, Schneekloth JS Jr, Yatsunyk LA Angew Chem Int Ed Engl. 2023 Jun 26;62(26):e202301666. doi: , 10.1002/anie.202301666. Epub 2023 Apr 25. PMID:36995904<ref>PMID:36995904</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Crystal structure of an i-motif from the HRAS promoter region
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